National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
1R01GM108921
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
3R01GM108921-03S1
United States
American Heart Association
17POST33671152
United States
Citation
Journal: Nat Commun / Year: 2018 Title: Cryo-EM structure of 5-HT receptor in its resting conformation. Authors: Sandip Basak / Yvonne Gicheru / Amrita Samanta / Sudheer Kumar Molugu / Wei Huang / Maria la de Fuente / Taylor Hughes / Derek J Taylor / Marvin T Nieman / Vera Moiseenkova-Bell / Sudha Chakrapani / Abstract: Serotonin receptors (5-HTR) directly regulate gut movement, and drugs that inhibit 5-HTR function are used to control emetic reflexes associated with gastrointestinal pathologies and cancer therapies. ...Serotonin receptors (5-HTR) directly regulate gut movement, and drugs that inhibit 5-HTR function are used to control emetic reflexes associated with gastrointestinal pathologies and cancer therapies. The 5-HTR function involves a finely tuned orchestration of three domain movements that include the ligand-binding domain, the pore domain, and the intracellular domain. Here, we present the structure from the full-length 5-HTR channel in the apo-state determined by single-particle cryo-electron microscopy at a nominal resolution of 4.3 Å. In this conformation, the ligand-binding domain adopts a conformation reminiscent of the unliganded state with the pore domain captured in a closed conformation. In comparison to the 5-HTR crystal structure, the full-length channel in the apo-conformation adopts a more expanded conformation of all the three domains with a characteristic twist that is implicated in gating.
History
Deposition
Oct 24, 2017
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Header (metadata) release
Feb 7, 2018
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Map release
Feb 7, 2018
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Update
Oct 23, 2024
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Current status
Oct 23, 2024
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec.
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK I / Details: blot for 2.5 sec..
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 2-39 / Number real images: 3550 / Average electron dose: 40.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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